TY - JOUR
T1 - How Can Static and Oscillating Electric Fields Serve in Decomposing Alzheimer's and Other Senile Plaques?
AU - Kalita, Surajit
AU - Bergman, Hagai
AU - Dubey, Kshatresh Dutta
AU - Shaik, Sason
N1 - Publisher Copyright:
© 2023 American Chemical Society.
PY - 2023/2/15
Y1 - 2023/2/15
N2 - Alzheimer's disease is one of the most common neurodegenerative conditions, which are ascribed to extracellular accumulation of β-amyloid peptides into plaques. This phenomenon seems to typify other related neurodegenerative diseases. The present study uses classical molecular-dynamics simulations to decipher the aggregation-disintegration behavior of β-amyloid peptide plaques in the presence of static and oscillating oriented external electric fields (OEEFs). A long-term disintegration of such plaques is highly desirable since this may improve the prospects of therapeutic treatments of Alzheimer's disease and of other neurodegenerative diseases typified by senile plaques. Our study illustrates the spontaneous aggregation of the β-amyloid, its prevention and breakdown when OEEF is applied, and the fate of the broken aggregate when the OEEF is removed. Notably, we demonstrate that the usage of an oscillating OEEF on β-amyloid aggregates appears to lead to an irreversible disintegration. Insight is provided into the root causes of the various modes of aggregation, as well as into the different fates of OEEF-induced disintegration in oscillating vs static fields. Finally, our simulation results are compared to the well-established TTFields and the Deep Brain Stimulation (DBS) therapies, which are currently used options for treatments of Alzheimer's disease and other related neurodegenerative diseases.
AB - Alzheimer's disease is one of the most common neurodegenerative conditions, which are ascribed to extracellular accumulation of β-amyloid peptides into plaques. This phenomenon seems to typify other related neurodegenerative diseases. The present study uses classical molecular-dynamics simulations to decipher the aggregation-disintegration behavior of β-amyloid peptide plaques in the presence of static and oscillating oriented external electric fields (OEEFs). A long-term disintegration of such plaques is highly desirable since this may improve the prospects of therapeutic treatments of Alzheimer's disease and of other neurodegenerative diseases typified by senile plaques. Our study illustrates the spontaneous aggregation of the β-amyloid, its prevention and breakdown when OEEF is applied, and the fate of the broken aggregate when the OEEF is removed. Notably, we demonstrate that the usage of an oscillating OEEF on β-amyloid aggregates appears to lead to an irreversible disintegration. Insight is provided into the root causes of the various modes of aggregation, as well as into the different fates of OEEF-induced disintegration in oscillating vs static fields. Finally, our simulation results are compared to the well-established TTFields and the Deep Brain Stimulation (DBS) therapies, which are currently used options for treatments of Alzheimer's disease and other related neurodegenerative diseases.
UR - http://www.scopus.com/inward/record.url?scp=85147446546&partnerID=8YFLogxK
U2 - 10.1021/jacs.2c12305
DO - 10.1021/jacs.2c12305
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C2 - 36735972
AN - SCOPUS:85147446546
SN - 0002-7863
VL - 145
SP - 3543
EP - 3553
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 6
ER -